scholarly journals Involvement of corticotropin-releasing factor in chronic stress regulation of the brain noradrenergic system.

1991 ◽  
Vol 88 (19) ◽  
pp. 8382-8386 ◽  
Author(s):  
K. R. Melia ◽  
R. S. Duman
2008 ◽  
Vol 198 (2) ◽  
pp. 403-417 ◽  
Author(s):  
Ellen H Stolte ◽  
Aurélia F de Mazon ◽  
Karen M Leon-Koosterziel ◽  
Maria Jesiak ◽  
Nic R Bury ◽  
...  

In higher vertebrates, mineralo- (aldosterone) and glucocorticoids (cortisol/corticosterone) exert their multiple actions via specific transcription factors, glucocorticoid (GR) and mineralocorticoid (MR) receptors. Teleostean fishes lack aldosterone and mineral regulatory processes seem under dominant control by cortisol. Despite the absence of the classical mineralocorticoid aldosterone, teleostean fishes do have an MR with cortisol and possibly 11-deoxycorticosterone (DOC) (as alternative for aldosterone) as predominant ligands. We studied corticoid receptors in common carp (Cyprinus carpio L). Through homology cloning and bioinformatic analysis, we found duplicated GR genes and a single MR gene. The GR genes likely result from a major genomic duplication event in the teleostean lineage; we propose that the gene for a second MR was lost. Transactivation studies show that the carp GRs and MR have comparable affinity for cortisol; the MR has significantly higher sensitivity to DOC, and this favours a role for DOC as MR ligand in fish physiology. mRNA of the GRs and the MR is expressed in forebrain (in pallial areas homologous to mammalian hippocampus), corticotrophin-releasing hormone (CRH) cells in the pre-optic nucleus (NPO) and pituitary pars distalis ACTH cells, three key neural/endocrine components of the stress axis. After exposure to prolonged and strong (not to mild acute) stressors, mRNA levels of both GRs and MR become down-regulated in the brain, but not in the NPO CRH cells or pituitary ACTH cells. Our data predicts a function in stress physiology for all CRs and suggest telencephalon as a first line cortisol target in stress.


2017 ◽  
Vol 39 (2) ◽  
pp. 98-105 ◽  
Author(s):  
Paula Madeira Fortes ◽  
Lucas Albrechet-Souza ◽  
Mailton Vasconcelos ◽  
Bruna Maria Ascoli ◽  
Ana Paula Menegolla ◽  
...  

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.


2018 ◽  
Vol 115 (43) ◽  
pp. E10187-E10196 ◽  
Author(s):  
Michael A. van der Kooij ◽  
Tanja Jene ◽  
Giulia Treccani ◽  
Isabelle Miederer ◽  
Annika Hasch ◽  
...  

Stringent glucose demands render the brain susceptible to disturbances in the supply of this main source of energy, and chronic stress may constitute such a disruption. However, whether stress-associated cognitive impairments may arise from disturbed glucose regulation remains unclear. Here we show that chronic social defeat (CSD) stress in adult male mice induces hyperglycemia and directly affects spatial memory performance. Stressed mice developed hyperglycemia and impaired glucose metabolism peripherally as well as in the brain (demonstrated by PET and induced metabolic bioluminescence imaging), which was accompanied by hippocampus-related spatial memory impairments. Importantly, the cognitive and metabolic phenotype pertained to a subset of stressed mice and could be linked to early hyperglycemia 2 days post-CSD. Based on this criterion, ∼40% of the stressed mice had a high-glucose (glucose >150 mg/dL), stress-susceptible phenotype. The relevance of this biomarker emerges from the effects of the glucose-lowering sodium glucose cotransporter 2 inhibitor empagliflozin, because upon dietary treatment, mice identified as having high glucose demonstrated restored spatial memory and normalized glucose metabolism. Conversely, reducing glucose levels by empagliflozin in mice that did not display stress-induced hyperglycemia (resilient mice) impaired their default-intact spatial memory performance. We conclude that hyperglycemia developing early after chronic stress threatens long-term glucose homeostasis and causes spatial memory dysfunction. Our findings may explain the comorbidity between stress-related and metabolic disorders, such as depression and diabetes, and suggest that cognitive impairments in both types of disorders could originate from excessive cerebral glucose accumulation.


2021 ◽  
pp. 1-12
Author(s):  
Merrill Singer ◽  
Merrill Singer

Children born into and raised in disadvantaged families tend to experience poorer health and more developmental delays, lower achievement, and a greater number of behavioural and emotional problems than children from wealthier homes. There is growing evidence that poverty and social inequality leave their imprint on brain structure as well. The brain exhibits considerable plasticity, one expression of which is shaped by the biology of inequality. A specific consequence is cognitive deficit found among children raised in poverty and subject to social discrimination. This paper argues that several pathways impacted by poverty, including chronic stress, malnutrition, exposure to heightened levels of air pollution, and other toxin exposures, syndemically link social inequality to underlying neural mechanisms and to suboptimal brain development and structure. These deficits need not be permanent and are reversible through urgently needed structural, socio-economic intervention.


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